The proposed research program focuses on the elucidation of the structures of the metal ion sites of metalloproteins, metalloenzymes, and other naturally-occurring metal cofactors and transporters. The major thrust of this research is to expand our understanding of the biological role of these metal ion-containing systems and to develop the chemical basis of their bilogical functions and reactivities. This research is based on a multifaceted approach utilizing modern spectroscopic methods (including electronic absorption, resonance Raman, and electron paramagnetic resonance spectroscopy), x-ray absorption and x-ray crystallographic structure determinations, and the synthesis, structural elucidation, and spectral characterization of inorganic complexes that serve as model systems. Studies are propsed on the binuclear iron proteins, hemerythrin and purple acid phosphatase. These systems have similar optical and magnetic properties and are believed to have a common structural element. For hemerythrin, the presence of a Mu-oxo bridge is well founded from previous crystallographic, spectroscopic, and EXAFS studies; vibrational spectroscopy will be used to verify the presence of such a bridging ligand in the phosphatase. For the physiologically-important oxy- and deoxy-forms of hemerythrin, higher resolution crystal data will be obtained. Blue copper proteins and Cu(II)-substituted alcohol dehydrogenase, which is a good analogue for type 1 copper sites, will be extensively studied by isotopically-substituted proteins to obtain rigorous experimental data for the interpretation of their resonance Raman spectra. The true origin of the Raman enhancement of these chromophores is not understood. The novel Ni-containing tetrapyrrole cofactor F430 will be investigated for its coordination chemistry and electronic structure in order to visualize its role in the enzymatic reduction of CD2 by methanogenic bacteria. Iron siderophores in cyanobacteria will be studied for novel hydroxamates and the mechanism of cellular iron uptake will be followed by observing the change in EPR intensity with uptake rates. Resonance Raman experiments are proposed to investigate the ionization states of the axial ligands of cytochrome P450 and to corroborate the identity of the sixth ligand as an alcoholic amino acid moiety. Finally, synthetic and spectroscopic investigations of multinuclear molybdenum complexes are planned.